دورية أكاديمية
أعرض في EDS

Preclinical characterization of A-582941: a novel alpha7 neuronal nicotinic receptor agonist with broad spectrum cognition-enhancing properties.

التفاصيل البيبلوغرافية
العنوان: Preclinical characterization of A-582941: a novel alpha7 neuronal nicotinic receptor agonist with broad spectrum cognition-enhancing properties.
المؤلفون: Tietje KR; Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064, USA., Anderson DJ, Bitner RS, Blomme EA, Brackemeyer PJ, Briggs CA, Browman KE, Bury D, Curzon P, Drescher KU, Frost JM, Fryer RM, Fox GB, Gronlien JH, Håkerud M, Gubbins EJ, Halm S, Harris R, Helfrich RJ, Kohlhaas KL, Law D, Malysz J, Marsh KC, Martin RL, Meyer MD, Molesky AL, Nikkel AL, Otte S, Pan L, Puttfarcken PS, Radek RJ, Robb HM, Spies E, Thorin-Hagene K, Waring JF, Ween H, Xu H, Gopalakrishnan M, Bunnelle WH
المصدر: CNS neuroscience & therapeutics [CNS Neurosci Ther] 2008 Spring; Vol. 14 (1), pp. 65-82.
نوع المنشور: Journal Article; Review
اللغة: English
بيانات الدورية: Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101473265 Publication Model: Print Cited Medium: Print ISSN: 1755-5930 (Print) Linking ISSN: 17555930 NLM ISO Abbreviation: CNS Neurosci Ther Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Oxford, UK : Wiley-Blackwell, c2008-
مواضيع طبية MeSH: Cognition/*drug effects , Nicotinic Agonists/*pharmacology , Pyridazines/*pharmacology , Pyrroles/*pharmacology , Receptors, Nicotinic/*physiology, Animals ; Humans ; alpha7 Nicotinic Acetylcholine Receptor
مستخلص: Among the diverse sets of nicotinic acetylcholine receptors (nAChRs), the alpha7 subtype is highly expressed in the hippocampus and cortex and is thought to play important roles in a variety of cognitive processes. In this review, we describe the properties of a novel biaryl diamine alpha7 nAChR agonist, A-582941. A-582941 was found to exhibit high-affinity binding and partial agonism at alpha7 nAChRs, with acceptable pharmacokinetic properties and excellent distribution to the central nervous system (CNS). In vitro and in vivo studies indicated that A-582941 activates signaling pathways known to be involved in cognitive function such as ERK1/2 and CREB phosphorylation. A-582941 enhanced cognitive performance in behavioral models that capture domains of working memory, short-term recognition memory, memory consolidation, and sensory gating deficit. A-582941 exhibited a benign secondary pharmacodynamic and tolerability profile as assessed in a battery of assays of cardiovascular, gastrointestinal, and CNS function. The studies summarized in this review collectively provide preclinical validation that alpha7 nAChR agonism offers a mechanism with potential to improve cognitive deficits associated with various neurodegenerative and psychiatric disorders.
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المشرفين على المادة: 0 (A-582941)
0 (Chrna7 protein, human)
0 (Nicotinic Agonists)
0 (Pyridazines)
0 (Pyrroles)
0 (Receptors, Nicotinic)
0 (alpha7 Nicotinic Acetylcholine Receptor)
تواريخ الأحداث: Date Created: 20080517 Date Completed: 20080801 Latest Revision: 20231011
رمز التحديث: 20231011
مُعرف محوري في PubMed: PMC6494002
DOI: 10.1111/j.1527-3458.2008.00037.x
PMID: 18482100
قاعدة البيانات: MEDLINE
الوصف
تدمد:1755-5930
DOI:10.1111/j.1527-3458.2008.00037.x